Objective To systematically evaluate the effect of exercise therapy on body structure,function,and activity and partici-pation in patients with chronic nonspecific neck pain(CNSNP)based on the International Classification of Func-tioning,Disability and Health(ICF)framework. Methods A PICO framework was constructed,and randomized controlled trials(RCTs)on the intervention of different types of exercise therapy for patients with CNSNP were retrieved from databases of CBM,Wanfang data,VIP,CNKI,Cochrane Library,Embase,PubMed and Web of Science,from the establishment to March,2024.The quality of the literature was evaluated with Cochrane Risk of Bias Tool and Physiotherapy Evidence Database(PEDro)scale,and the evidence quality of the outcome indicators was evaluated using GRADE.Data were syn-thesized and analyzed using RevMan 5.3,and the risk of bias was evaluated using Stata 18.0. Results A total of eleven RCTs involving 668 subjects were included.The scores of PEDro scale were five to eight.The types of interventions included muscle strength training,stability training,proprioception training,Yoga and Pi-lates.The control groups received placebo,physical factor therapy and health education.Exercise therapy could increase the craniovertebral angle(SMD=0.84,95%CI 0.42 to 1.26,P<0.001),reduce the Visual Analogue Scale score(SMD=-2.05,95%CI-2.58 to-1.52,P<0.001),increase the pressure pain threshold(MD=112.27,95%CI 75.03 to 149.50,P<0.001),increase the range of motion of cervical forward(SMD=1.24,95%CI 0.34 to 2.15,P=0.007)and lateral(SMD=1.52,95%CI 0.40 to 2.65,P=0.008)flexion,and improve the endurance of the deep cervical flexors(SMD=1.02,95%CI 0.10 to 1.94,P=0.03)and position sense of the cervical spine(SMD=-1.00,95%CI-1.47 to-0.53,P<0.001);however,it was not significant in improving the range of motion of backward flexion(SMD=0.85,95%CI-1.04 to 2.75,P=0.38)and rotation(SMD=1.65,95%CI-0.35 to 3.65,P=0.11).Exercise therapy could also reduce the Neck Disability Index score(MD=-11.88,95%CI-16.09 to-7.68,P<0.001),and it was no significant in the Short-Form-36 score(MD=19.04,95%CI-3.00 to 41.08,P=0.09). Conclusion Exercise therapy can improve head posture,pain,motion of forward flexion and lateral flexion,endurance of the cervical flexors and joint position sense,and the overall function in patients with CNSNP.However,fur-ther researches are needed to verify the effects on cervical backward flexion and rotation,and quality of life.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Purpose To explore the application value of clinical-ultrasound parameter model in secondary hyperparathyroidism(SHPT).Materials and Methods A total of 86 patients(134 lesions)with renal insufficiency who underwent maintenance hemodialysis in the First Affiliated Hospital of Shihezi University from October 2020 to August 2022 were included and divided into group 1 according to the level of parathyroid hormone(iPTH)(iPTH＜300 pg/ml),group 2(iPTH 300-800 pg/ml)and group 3(iPTH≥800 pg/ml),all patients underwent gray-scale parathyroid ultrasound and acoustic palpation tissue quantitative imaging examinations.The characteristics of glandular gray-scale ultrasound and virtual touch tissue imaging quantification parameters between different groups,combined with relevant clinical indicators,established a clinical-ultrasound parameter model,used multiple linear regression to analyze the correlation between the model and iPTH,explored the independent risk factors of iPTH,and evaluated this model to evaluate SHPT the value of.Results There were significant differences in dialysis age,phosphorus,alkaline phosphatase,serum creatinine,corrected calcium and phosphorus product,lesion size,number,echo,shear wave velocity(SWV)max,SWVcen,and SWVmean among the three groups(F/x2/H=6.396-53.524,all P＜0.05).Dialysis age,phosphorus,alkaline phosphatase,and SWVratio were independent influencing factors of iPTH level(β=0.514,0.422,0.226,-0.368,all P＜0.005).The area under the curve,sensitivity,specificity and accuracy of the model for diagnosing SHPT and predicting surgical treatment with iPTH levels of 300 pg/ml and 800 pg/ml were 0.967,95.00％,100.00％,97.73％and 0.824,77.42％,71.43％and 90.00％,respectively.Conclusion Dialysis age,phosphorus,alkaline phosphatase and SWVratio are independent influencing factors of iPTH level,and the clinical-ultrasound parameter model is of great value in accurately assessing the severity of SHPT.

Although chromosomal mosaic embryos detected by trophectoderm(TE)biopsy offer healthy embryos available for transfer,high-resolution postnatal karyotyping and chromosome testing of the transferred embryos are insufficient.Here,we applied single-cell multi-omics sequenc-ing for seven infants with blastula chromosomal mosaicism detected by TE biopsy.The chromo-some ploidy was examined by single-cell genome analysis,with the cellular identity being identified by single-cell transcriptome analysis.A total of 1616 peripheral leukocytes from seven infants with embryonic chromosomal mosaicism and three control ones with euploid TE biopsy were analyzed.A small number of blood cells showed copy number alterations(CNAs)on seem-ingly random locations at a frequency of 0％-2.5％per infant.However,none of the cells showed CNAs that were the same as those of the corresponding TE biopsies.The blastula chromosomal mosaicism may be fully self-corrected,probably through the selective loss of the aneuploid cells dur-ing development,and the transferred embryos can be born as euploid infants without mosaic CNAs corresponding to the TE biopsies.The results provide a new reference for the evaluations of trans-ferring chromosomal mosaic embryos in certain situations.

Objective:To investigate the present situation of unintended pregnancy within two years postpartum and its influencing factors in China.Methods:Participants who delivered a live birth at 60 hospitals in 15 provinces in the eastern, central and western regions of China during July 2015 to June 2016 were interviewed by using structured questionnaire. Information on occurrence of unintended pregnancy within 2 years after delivery, postpartum contraceptive use, sexual resumption, breastfeeding, and women′s socio-demographic characteristics, and so on, were collected. Life-table analysis, cluster log-rank tests and a 2-level Cox regression model were used for data analysis.Results:A total of 18 045 postpartum women were investigated. The cumulative 1- and 2-year unintended pregnancy rates after delivery were 5.3% (95% CI: 4.5%－6.1%) and 13.1% (95% CI: 11.3%－14.8%), respectively. Cox regression model analysis showed that the risk of unintended pregnancy within 2 years postpartum were increased in younger women, ethnic minorities, women with abortion history, and those who had a vaginal delivery with short lactation time and late postpartum contraceptive initiation (all P<0.01). The risk of postpartum unintended pregnancy was not associated with geographic regions and hospitals where women gave a birth (all P>0.05). Conclusions:In China, the risk of unintended pregnancy within 2 years after delivery is relatively high. Service institutions and service providers should improve the quality of postpartum family planning services, promote the use of high effect contraceptive methods, and educate women to use a method at the time of their sexual resumption or even before.

Objective:To study the non-target metabolomics analysis and to analyze the metabolomic changesof cerebrospinal fluid (CSF) in patients with tuberculous meningitis.Methods:Case-control study. From July 2018 to July 2019, 20 cerebrospinal fluid specimens of diagnosed patients with tuberculous meningitis were collectedin the department of neurology from the first medical center of the PLA general hospital and the eighth medical center of the PLA general hospital and 20 CSF without tuberculous meningitis as the control. Among them, there were 12 males and 8 femalesin the tuberculous meningitis group, aged (37.9±16.1) years; there were 13 males and 7 femalesin the control group, aged (34.7±14.8) years. Using ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) technology with three different mode, namely reverse phase chromatography positive ion mode, reverse phase chromatography negative ion mode and hydrophilic chromatography positive ion mode,to detectthe metabolic fingerprints of patients′CSF and analyzed by SIMCA software for orthogonal partial least squares discriminant analysis (OPLS-DA). The variable importance projection value of OPLS-DA model (threshold value>1) plus the P value of t-test (P<0.05) was applied to find the differential metabolites in the cerebrospinal fluid of the two groups of patients.Results:Ten differential metabolites were found in CSF, including L-isoleucine, L-phenylalanine, L-kynurenine, L-methionine, L-tyrosine acid, dimethylglycine, L-alanine, L-threonine, L-histidine and L-lysine, and all of them were up-regulated in the tuberculous meningitis group.Conclusion:Changesof the amino acid metabolism found in the cerebrospinal fluid of tuberculous meningitis patients can provide basis for differential diagnosis and basic molecular research of tuberculous meningitis.

OBJECTIVE： To investigate the effects of Kangfuxin liquid on repairing cartilage defect model of knee osteoarthritis （KOA） in rabbits and its mechanism. METHODS： Totally 72 male New Zealand rabbits were selected and randomly divided into model control group and Kangfuxin low-dose， medium-dose， high-dose groups， with 18 rabbits in each group. A cartilage defect model of the medial femoral condyle of the right knee joint in rabbits was established by drilling after anesthesia surgery. Then the rabbits in each group were given medicine via articular cavity immediately. Kangfuxin low-dose， middle-dose and high-dose groups were given 20％， 40％， 80％ Kangfuxin liquid； model control group was given constant volume of normal saline consecutively， 0.2 mL/kg， once every 3 days. At 4th， 8th， 12th week after medication， the wound repair of cartilage defect in rabbits was observed. Immediately after medication and at 4th， 8th， 12th week after medication， repaired tissue of cartilage defect in rabbits was scored histologically with Wakitani scoring standard under light microscope. At 12th week after medication， pathological changes of repaired tissue of cartilage defect in rabbits were observed by Masson staining. The levels of NO， SOD and LPO in joint fluid and PYD in urine of rabbits were detected by ELISA. RESULTS： At 4th， 8th， 12th week after medication， compared with model control group， cartilage defects in rabbits were repaired well in Kangfuxin low-dose， medium-dose and high-dose groups. At 4th， 8th， 12th week after medication， compared with immediately after medication and model control group at same time point， histomorphological score of repairing cartilage defect of knee joint in rabbits decreased significantly in Kangfuxin low-dose， medium-dose and high-dose groups （P＜0.05）. At 12th week after medication， compared with model control group， the histopathology degree of cartilage defect of knee joint in rabbits was significantly alleviated in Kangfuxin low-dose， medium-dose and high-dose groups. At 4th， 8th， 12th week after medication， compared with model control group， the levels of NO and LPO in joint fluid and PYD level in urine were decreased to different extent in Kangfuxin low-dose， medium-dose and high-dose groups， while SOD level was increased to different extent； at 12th week after medication， the difference of each index has statistical significance （P＜0.05 or P＜0.01）. CONCLUSIONS： Kangangxin liquid can significantly repair cartilage defect of KOA cartilage defect model rabbits， the mechanism of which may be associated with increasing the expression of SOD and mediating NO-inhibited chondrocyte apoptosis.

Cystic echinococcosis (CE), a zoonotic disease caused by Echinococcus granulosus at the larval stage, predominantly develops in the liver and lungs of intermediate hosts and eventually results in organ malfunction or even death. The interaction between E. granulosus and human body is incompletely understood. Exosomes are nanosized particles ubiquitously present in human body fluids. Exosomes carry biomolecules that facilitate communication between cells. To the best of our knowledge, the role of exosomes in patients with CE is not reported. Here, we isolated exosomes from the sera of patients with CE (CE-exo) and healthy donors and subjected them to liquid chromatography-tandem mass spectrometry analysis. Proteomic analysis identified 49 proteins specifically expressed in CE-exo, including 4 proteins of parasitic origin. The most valuable parasitic proteins included tubulin alpha-1C chain and histone H4. And 8 proteins were differentially regulated in CE-exo (fold change>1.5), as analyzed with bioinformatic methods such as annotation and functional enrichment analyses. These findings may improve our understanding about the interaction between E. granulosus and human body, and may contribute to the diagnosis and prevention of CE.
Computational Biology ; Diagnosis ; Echinococcosis ; Echinococcus granulosus ; Echinococcus ; Exosomes ; Gene Ontology ; Histones ; Human Body ; Humans ; Liver ; Lung ; Mass Spectrometry ; Tissue Donors ; Tubulin ; Zoonoses

Objective To analyze the characteristics of alcohol-related brain damage according to 18F-fluorodeoxy-glucose (18F-FDG) position emission tomography-computer tomography (PET-CT).Methods Excessive alcohol consumption patients accepted 18F-FDG PET-CT in our hospital from August 2016 to November 2018 were chosen as excessive alcohol consumption group and non-drinking patients accepted 18F-FDG PET-CT in our hospital at the same time were chosen as non-drinking group according to 1:4 ratio.The 18F-FDG PET-CT imaging data were analyzed;the characteristics of abnormal changed rate of CT sequences after stratification by age and the relations of alcohol consumption with abnormal CT sequences and PET sequences were compared between the two groups.Results A total of 52 patients with excessive alcohol consumption and 200 non-drinking patients were chosen.Among patients aged 45-59 years,the abnormal changed rate of CT sequences in the excessive alcohol consumption group was significantly higher than that in the non-drinking group (P＜0.05).In the CT sequences,33 patients in the 2 groups presented abnormalities,mainly including cerebral atrophy and lacunar infarction.In the PET sequences,62 patients in the two groups presented abnormalities,mainly manifesting as reduced metabolism level of bilateral frontal and parietal lobes.Among the 52 patients from excessive alcohol consumption group,those with abnormal CT sequences were older,had longer drinking history and had higher total drinking amount than those with normal CT sequences,and the differences were statistically significant (P＜0.05).As compared with those in patients with normal PET sequences,those with abnormal PET sequences had higher weekly and total alcohol consumption,and longer drinking history,and the differences were statistically significant (P＜0.05).Conclusion Excessive alcohol consumption is an important risk factor for structural damages in middle-aged men,which can cause a decrease of glucose metabolism level in the frontal and parietal lobes.

Objective: To analyze the interpretation results on the pathogenic classification of KCNH2 variants and SCN5A variants of long QT syndrome (LQTS) based on American College of Medical Genetics and Genomics (ACMG) guidelines by 4 clinical gene screening agencies from Beijing. Methods: Pathogenic classification of 16 variants in KCNH2 and SCN5A was made by 4 clinical gene screening agencies from Beijing based on ACMG guideline. Krippendorff's alpha was used to assess the inter-agency variation consistency. Results: All 4 agencies made pathogenic assessment on all the variants and provided the interpretation results for the classification. For the eight variants from the patients with LQTS, the consistency of classification was only 1/8 and the alpha test value was - 0.01. For the eight variables from incidental findings, the consistency of classification was 4/8 and the alpha test value was 0.407. Evidence analysis of the 4 variants with large differences in classification among agencies showed that the main reasons for the discrepancies originated from the comprehensiveness of the literature search and the inconsistency of the subjective determination of the evidence grade. Conclusion The consistency of the pathogenic classification of LQTS gene variants based on ACMG guidelines among clinical gene screening agencies from Beijing is poor, which will result in great impact on the clinical treatment strategies of the patients with LQTS. The standardization of pathogenic evaluation of variants in clinical gene screening agencies needs to be improved urgently.